Publications by authors named "Metroka C"

Article Synopsis
  • Researchers conducted a genome-wide association study focusing on HIV-1 controllers and progressors to understand genetic factors influencing chronic viral infections.
  • They discovered over 300 significant single-nucleotide polymorphisms (SNPs) specifically within the major histocompatibility complex (MHC), emphasizing its importance for infectious diseases.
  • Key findings indicate that specific amino acids in HLA proteins, especially HLA-B and HLA-C, significantly influence the interaction between HLA and viral peptides, affecting the control of HIV infection.
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Both HIV and its treatment, particularly protease inhibitors, can cause lipidemia similar to that seen with the metabolic syndrome. The most notable effects are elevated triglyceride levels and decreased high-density lipoprotein cholesterol levels, with or without elevated low-density lipoprotein cholesterol (LDL-C) levels. Current recommendations by the National Cholesterol Education Program for HIV-infected persons focus on LDL-C as the primary target of therapy: after lifestyle modifications, statins should be used to lower LDL-C levels.

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Rta, the gene product of Kaposi's sarcoma-associated herpesvirus (KSHV) encoded mainly in open reading frame 50 (ORF50), is capable of activating expression of viral lytic cycle genes. What was not demonstrated in previous studies was whether KSHV Rta was competent to initiate the entire viral lytic life cycle including lytic viral DNA replication, late-gene expression with appropriate kinetics, and virus release. In HH-B2, a newly established primary effusion lymphoma (PEL) cell line, KSHV ORF50 behaved as an immediate-early gene and autostimulated its own expression.

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Human herpesvirus 8 (HHV-8) infection has been implicated in the etiology of Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD), three diseases that frequently develop in immunocompromised, human immunodeficiency virus-positive individuals. One hypothesis that would account for different pathological manifestations of infection by the same virus is that viral genes are differentially expressed in heterogeneous cell types. To test this hypothesis, we analyzed the localization and levels of expression of two viral genes expressed in latent and lytic infections and the viral homologue of interleukin-6 (vIL-6).

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Previous analysis of the majority of Kaposi's sarcoma (KS) tumors, in both AIDS and non-AIDS populations, has revealed the consistent presence of two small subsegments (open reading frame 25/26 [ORF25/26] and ORF75) of a novel human gamma class herpesvirus genome referred to as KSHV or HHV-8. We have carried out DNA sequence comparisons with DNAs encompassing a total of 2,500 bp each over three separate PCR-amplified fragments from KS lesions and body cavity-based lymphoma (BCBL) samples from 12 distinct patients, including four African and two classical or endemic non-AIDS KS samples. The results revealed differences at 37 of 2,500 nucleotide positions (i.

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Background: The recent identification in patients with Kaposi's sarcoma of DNA sequences with homology to gammaherpesviruses has led to the hypothesis that a newly identified virus, Kaposi's sarcoma-associated herpeslike virus (KSHV), has a role in the pathogenesis of Kaposi's sarcoma. We developed serologic markers for KSHV infection.

Methods: KSHV antigens were prepared from a cell line (BC-1) that contains the genomes of both KSHV and the Epstein-Barr virus (EBV).

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We conducted a Phase I trial to evaluate the safety, maximally tolerated dose (MTD), antitumor activity, and pharmacology of once-weekly oral etoposide in patients with Kaposi's sarcoma (KS) and AIDS. From September 1990 to October 1991, 27 eligible patients with biopsy-confirmed KS were treated at six etoposide dose levels, ranging from 150 to 400 mg weekly. Patients were treated until their tumor progressed or until unacceptable toxicity developed.

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Objective: --To ascertain if low-dose multiagent chemotherapy, with central nervous system prophylaxis and antiretroviral therapy, might be associated with increased efficacy and decreased risk of intercurrent infection in patients with malignant lymphoma related to the acquired immunodeficiency syndrome (AIDS).

Design: --A phase II prospective clinical trial, with median follow-up of 33 months.

Setting: --Eight university hospitals, within the context of the AIDS Clinical Trials Units, sponsored by the National Institute of Allergy and Infectious Diseases.

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Despite numerous reports suggesting an association of Hodgkin's disease (HD) with the acquired immunodeficiency syndrome (AIDS), HD in an individual seropositive for the human immunodeficiency virus (HIV) still is not considered a criterion for the diagnosis of AIDS. The authors report 23 new cases of HD in individuals at risk for AIDS and review the literature. As a group, individuals at risk for AIDS who develop HD have a more aggressive form of the illness (82% with stage III or IV), have or develop AIDS-related opportunistic infections (54%), second neoplasms (10%), and /or profound cytopenias (32%), and 85 to 90% are HIV positive when tested.

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With the growing number of patients with the acquired immunodeficiency syndrome there has been a marked increase in the incidence of Kaposi's sarcoma. Kaposi's sarcoma of the penis was the initial presenting manifestation of acquired immunodeficiency syndrome in 4 patients. Overall, less than 3% of all acquired immunodeficiency syndrome patients with Kaposi's sarcoma have the initial lesion on the penis.

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The availability of uniform and precise criteria for disease evaluation, response to treatment, and clinical staging of Kaposi's sarcoma (KS) in individuals with the acquired immune deficiency syndrome (AIDS) would facilitate therapeutic trials in patients with this neoplasm. Recently, a group of oncologists conducting clinical trials in patients with AIDS-associated KS as part of a cooperative group established by the National Institute of Allergy and Infectious Diseases (NIAID) drafted such criteria. The criteria take into account the unique problems associated with the evaluation of patients with a disseminated cutaneous neoplasm in the setting of a systemic virus infection associated with immune deficiency.

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Seventy-four sequential lymph node biopsies from 30 acquired immunodeficiency syndrome (AIDS)/AIDS-related complex (ARC) patients showed temporal histologic progression from explosive follicular hyperplasia (EFH) to mixed follicular hyperplasia/involution (mixed) to follicular involution (FI) to lymphocyte depletion (LD). This histologic progression correlated with symptoms, development of opportunistic infections (OI), and mortality. At initial biopsy, only 50% of the AIDS/ARC patients with EFH/mixed compared to 100% with FI/LD were symptomatic with weight loss, night sweats, diarrhea, fever, or fatigue.

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AL-721 is a lipid compound composed of neutral lipids, phosphatidylcholine and phosphatidylethanolamine in a 7:2:1 ratio. The objective of this open study was to evaluate the effects of AL-721 in vivo in an 8-week open trial in which 10 g twice daily was administered on a low fat diet to eight HIV-infected subjects with lymphadenopathy syndrome (LAS). Serial lymphocyte cocultivation studies in 7 patients with initial culture positivity appeared to demonstrate reduction of reverse transcriptase peak counts in 5 with the trough noted in 4 at 8 weeks and in one at 4 weeks following termination of therapy.

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Cytogenetic studies were performed on direct and 24-hour culture preparations of eight lymph node biopsies from seven patients with acquired immunodeficiency syndrome (AIDS) or AIDS-related complex (ARC)-associated lymphadenopathy in whom histological evidence of lymphoma was not detected. Three of these seven had chromosomal abnormalities, including chromosome instability in one and clonal chromosomal abnormalities in two; one of the latter was a t(8;14)(q24;q32). The remaining five showed normal karyotypes.

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Malignant lymphomas occurring in 29 homosexual men and one thalassemic woman with the acquired immunodeficiency syndrome or the acquired immunodeficiency syndrome-related complex are reported using a working formulation for non-Hodgkin's lymphomas (NHLs). The patients' ages ranged from 25 to 59 years, with an average age of 42 years. Ninety percent of the cases were extranodal; 67% were exclusively extranodal.

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We report the pathologic findings in specimens submitted for histologic and cytologic evaluation from 67 patients with the acquired immunodeficiency syndrome. A wide variety of opportunistic pathogens were identified in 41 patients. Mycobacterium avium-intracellulare evoked only a mild host response: granulomas, if present, were poorly formed.

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